This project is in collaboration with Dr. Silvano Preciuttini, from the University of Pisa. Dr. Presciuttini and his colleagues in Italy have identified a large pedigree that exhibits high frequency of colorectal cancer across 5 generations, that fits the criteria for Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and that does not appear to have mutations in several known genes for HNPCC. In collaboration with Drs. Francis Collins and Steven Lipkin of NHGRI, this family has been genotyped for markers in the regions of all other known genes for HNPCC and linkage analysis has been performed by Drs. Presciuttini and Bailey-Wilson. These analyses have shown evidence that the colorectal cancer gene in this family is not linked to these other known loci. This family has now been typed in a genome wide screen to look for a new gene predisposing to colorectal cancer. Analyses of these genome-screen data are ongoing. Additional family members have been sampled and we plan to genotype these family members to increase power to detect linkage, thus allowing follow-up of intriguing regions from the genome wide screen.